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Metronidazole
Nimorazole
Ornidazole
Secnidazole
Tinidazole

Nitroimidazoles

The imidazoles are remarkable in that they cover bacteria, fungi, viruses, protozoa, and helminths. Outside the antimicrobial field certain imidazoles have been shown to exhibit radiosensitizing properties and have attracted attention as adjuncts to radiation therapy for some tumours.

The members of this family of compounds used as antibacterial agents are 5-nitroimidazoles, of which metronidazole (Figure 1) is the best known. Related 5-nitroimidazoles include tinidazole, ornidazole, secnidazole, and nimorazole; they share the properties of metronidazole but have longer plasma half-lives.

Figure 1. Chemical structure of metronidazole

Metronidazole was initially used to treat trichomoniasis, and later for two other protozoal infections amoebiasis and giardiasis. The antibacterial activity of the compound was first identified when a patient affected by acute ulcerative gingivitis resolved spontaneously while receiving metronidazole for a Trichomonas vaginalis infection. Anaerobic bacteria are commonly incriminated in gingivitis, and it was subsequently demonstrated that metronidazole possesses potent antibacterial activity that was originally thought to be confined to strict anaerobes since even oxygen-tolerant species such as Actinomyces and Propionibacterium are resistant. However, some microaerophilic bacteria, including Gardnerella vaginalis and Helicobacter pylori, are susceptible to nitroimidazoles that are used in the treatment of infections with these organisms.

Metronidazole is very effective against anaerobic bacteria and resistance is uncommon therefore it is the drug of choice for the treatment of anaerobic infections. It is commonly used for prophylaxis in some surgical procedures in which postoperative anaerobic infection is a frequent complication. It is the cheapest alternative to vancomycin in the treatment of antibiotic-associated colitis caused by Clostridium difficile toxins.

The specific activity against anaerobes resides in the fact that a reduction product is produced intracellularly exclusively under anaerobic conditions. The reduced form of metronidazole is thought to induce breakage in the DNA strand by a mechanism that has not been completely determined.

The 5-nitroimidazoles are generally free from serious side effects, though gastrointestinal upset is common. Since these drugs act on DNA they are potentially genotoxic and tumorigenic, but there is no evidence that these problems have arisen despite widespread clinical use.

 

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